Enhanced Oral Bioavailability and Improved Biological Activities of a Quercetin/Resveratrol Combination Using a Liquid Self-Microemulsifying Drug Delivery System

Abstract

Both quercetin and resveratrol are promising plant-derived compounds with various well-described biological activities; however, they are categorized as having low aqueous solubility and labile natural compounds. The purpose of the present study was to propose a drug delivery system to enhance the oral bioavailability of combined quercetin and resveratrol. The suitable self-microemulsifying formulation containing quercetin together with resveratrol comprised 100 mg Capryol 90, 700 mg Cremophor EL, 200 mg Labrasol, 20 mg quercetin, and 20 mg resveratrol, which gave a particle size of 16.91 ± 0.08 nm and was stable under both intermediate and accelerated storage conditions for 12 months. The percentages of release for quercetin and resveratrol in the self-microemulsifying formulation were 75.88 ± 1.44 and 86.32 ± 2.32%, respectively, at 30 min. In rats, an in vivo pharmacokinetics study revealed that the area under the curve of the self-microemulsifying formulation containing quercetin and resveratrol increased approximately ninefold for quercetin and threefold for resveratrol compared with the unformulated compounds. Moreover, the self-microemulsifying formulation containing quercetin and resveratrol slightly enhanced the in vitro antioxidant and cytotoxic effects on AGS, Caco-2, and HT-29 cells. These findings demonstrate that the self-microemulsifying formulation containing quercetin and resveratrol could successfully enhance the oral bioavailability of the combination of quercetin and resveratrol without interfering with their biological activities. These results provide valuable information for more in-depth research into the utilization of combined quercetin and resveratrol.

Fabrication and In Vitro/Vivo Evaluation of Drug Nanocrystals Self-Stabilized Pickering Emulsion for Oral Delivery of Quercetin

“…Nonetheless, QT exhibits poor dissolution behavior due to its low solubility that is only 0.01 mg·mL −1 in water at 25 °C [ 10 ], which seriously limited its oral bioavailability. In the past few decades, considerable research efforts have been devoted to enhancing the solubility of QT in water, thus improving its oral bioavailability, such as liposomes [ 11 ], self-microemulsion [ 12 ], and nanocrystals [ 13 , 14 , 15 ]). But these methods still have some limitations such as poor stability and low drug loading capacity.…”

Co-encapsulation of quercetin and resveratrol in zein/carboxymethyl cellulose nanoparticles: characterization, stability and in vitro digestion

“…18 Therefore, researchers are working to improve the gastrointestinal stability and bioavailability of quercetin and resveratrol, which is often achieved using encapsulation technologies. [19][20][21] Chitosan-coated liposomes have been used to improve the acid resistance and bioavailability of quercetin and resveratrol. 21 Self-nanoemulsifying drug delivery systems have been used to encapsulate, protect, and release resveratrol, quercetin, and genistein, with the objective of creating nutraceutical treatments for breast cancer.…”

Enhancing Bioavailability of Nutraceutically Used Resveratrol and Other Stilbenoids

“…This can alter the duration of therapeutic activity and the bioavailability [ 100 ]. Stilbenoids can be delivered by different types of systems [ 101 ], namely, microspheres [ 102 ], microcapsules [ 103 ], self-emulsifying drug delivery system (SEDDS) [ 101 , 104 ], self-microemulsifying drug delivery system (SMEDDS) [ 105 , 106 , 107 ], nanosponges [ 108 ], nanoemulsions [ 109 , 110 ], self-nanoemulsifying drug delivery system (SNEDDS) [ 111 , 112 , 113 , 114 ], self-double-emulsifying drug delivery system (SDEDDS) [ 115 ], liposomes [ 116 , 117 ], nanoparticles [ 118 , 119 , 120 , 121 , 122 , 123 , 124 , 125 , 126 ], nanostructured lipid carriers [ 127 ], nanosuspensions [ 128 ], chitosan–gellan nanofiber [ 129 ], solidified phospholipid complex [ 130 ], spiral dextrin [ 131 ], and buccal cyclodextrin delivery system [ 132 ]. All delivery systems are extensively studied, but there is little clinical data.…”